the limited ability to change the environment and 3D animal motion make it difficult to assess dynamic phenotypes other than rough motion analysis. In contrast, microfluidics, with relevant length scales down to the animal's size, offers improved means to handle small animals and control their environment. [10][11][12][13][14] Animals can be confined in 2D or even immobilized, and liquids can be exchanged rapidly. These approaches enable advanced functional assays such as monitoring brain activity [15,16] or performing high-resolution behavior. [17] However, most of the highthroughput screening techniques are end-point assays based on fluorescence images [18,19] and do not translate well for phenotyping based on functional imaging. Single-phase microfluidic systems, although powerful, have limitations in the number of animals they can handle [17,[20][21][22][23] and the ability to modulate the experimental conditions at will. [16,[23][24][25] Multiphase microfluidics has unique attributes that make it well suited to tackle these challenges. These include the ability to partition, create independent containers of various sizes, generate precise chemical environments, perform serial processing, and consume ultra-low amounts of reagents. Multiphase microfluidics has led to advanced screening technologies impacting a broad range of disciplines, from particle synthesis [26,27] and synthetic biology, [28,29] to drug discovery, [30,31] and research in fundamental biology. [32,33] It has been applied successfully for numerous single-cell screens [34] and is gaining popularity for multicellular organisms such as spheroids and organoids. [35][36][37][38] In contrast, the development of multiphase microfluidics techniques for small animals [39][40][41][42][43] has seen a slow progress because of several technical bottlenecks. For instance, passive encapsulation techniques [44] are not adaptable to motile, multi-cellular organisms, mining the throughput. Second, techniques for controlling the droplet composition post-production rely mainly on merging, [45] which limits the ability to dynamically alter the droplet content. Furthermore, advanced active droplet manipulation tools [46][47][48][49] are inadequate as mechanical, thermal, and electrical-induced forces may create undesired stimulation. [50][51][52] Addressing these limitations is critical to fully exploit the potential of multiphase microfluidics as smallanimal screening technology.Here we describe a multiphase microfluidic platform to screen dynamic phenotypes in small animals. We demonstrate the use of this platform with the nematode C. elegans, Screening functional phenotypes in small animals is important for genetics and drug discovery. Multiphase microfluidics has great potential for enhancing throughput but has been hampered by inefficient animal encapsulation and limited control over the animal's environment in droplets. Here, a highly efficient single-animal encapsulation unit, a liquid exchanger system for controlling the droplet chemical environment dynami...